Currently, there is no effective vaccine to prevent several clinically important chronic viral infections, including cytomegalovirus (CMV), herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infection. The primary goal of this proposal is to determine whether co-administration of adjuvant recombinant human interleukin-I 2 (rhIL-12) with a live, attenuated viral vaccine of known immunogenicity to healthy, uninfected adults can safely enhance their virus-specific CD8+ cytotoxic T lymphocyte (CTL) and T helper lymphocyte type 1 (TH1)-type immune responses, as well as their virus-specific neutralizing antibody responses. An important secondary objective will focus on determining the optimally safe and effective dose of adjuvant rhIL-12. We propose to accomplish these aims by combining a live, attenuated CMV vaccine (Towne strain) with rhIL-12. CMV is an important cause of morbidity and mortality in newborn children and in immunocompromised individuals. We will use cytokine flow cytometry CFC) and neutralizing antibody assays to measure CMV-specific immunologic responses in CMV-uninfected volunteers who are randomized to receive the Towne human CMV strain vaccine with or without rhIL-12. To quantify CMV-specific CTL's, a novel method of stimulating PBMC's short-term with short overlapping peptides of a dominant, antigen target for CMV-specific CTL's will be employed with CFC to quantify CMV-specific, CD8+/IFNg+T lymphocytes. The proposed work involves a Phase I, randomized, double-blind, placebo-controlled, dose-escalation study design. Up to 48 medically stable, healthy, CMV-seronegative adults (age range 18-45 years old) will receive 1 x 10E3.47 pfu of the Towne CMV vaccine as a subcutaneous (SC) injection. The range of rhIL-12 doses to be explored will be 0.5, 1.0, 2.0 and 4.0 mg. At each rhIL-12 dose level, 12 subjects will be randomly assigned in a 3:1 manner to receive either active rhIL-12 or matching placebo as a SC injection simultaneously with Towne vaccine. If no more than one subject has had a Grade 3 or higher adverse event at a given dose level, then enrollment of the next, higher rhIL-12 dose group will begin. If adjuvant rhIL-12 is safe and does enhance in vitro anti-CMV immune responses to this vaccine, then further studies will be indicated to determine if combined viral vaccine/adjuvant rhIL-12 vaccination strategies can enhance protective efficacy in preventing serious chronic viral infections for which cell-mediated immune response (and CTL in particular) is key to protective immunity and for which effective vaccines do not exist (e.g. CMV, HSV and HIV).